Discovery, SAR Study of GST Inhibitors from a Novel Quinazolin-4(1H)-one Focused DNA-Encoded Library
文献类型：期刊论文
| 作者 | Wen, Xin1,2; Zhang, Minmin1,2 ; Duan, Zhiqiang1; Suo, Yanrui1,2; Lu, Weiwei1; Jin, Rui1; Mu, Baiyang1; Li, Kaige1; Zhang, Xu1,2; Meng, Linghua1,2
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| 刊名 | JOURNAL OF MEDICINAL CHEMISTRY
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| 出版日期 | 2023-08-08 |
| 页码 | 15 |
| ISSN号 | 0022-2623 |
| DOI | 10.1021/acs.jmedchem.2c02129 |
| 通讯作者 | Shen, Aijun(shenaj@simm.ac.cn) ; Lu, Xiaojie(xjlu@simm.ac.cn) |
| 英文摘要 | The DNA-encoded library (DEL) is a powerful hit-generationtoolin drug discovery. This study describes a new DEL with a privilegedscaffold quinazolin-4(3H)-one developed by a robustDNA-compatible multicomponent reaction and a series of novel glutathione S-transferase (GST) inhibitors that were identified throughaffinity-mediated DEL selection. A novel inhibitor 16 was subsequently verified with an inhibitory potency value of 1.55 & PLUSMN; 0.02 & mu;M against SjGST and 2.02 & PLUSMN; 0.20 & mu;M againsthGSTM2. Further optimization was carried out via various structure-activityrelationship studies. And especially, the co-crystal structure ofthe compound 16 with the SjGST was unveiled, which clearlydemonstrated its binding mode was quite different from the known GSH-likecompounds. This new type of probe is likely to play a different rolecompared with the GSH, which may provide new opportunities to discovermore potent GST inhibitors. |
| WOS关键词 | GLUTATHIONE-S-TRANSFERASES ; STRATEGIES ; DERIVATIVES ; REFINEMENT ; BINDING |
| 资助项目 | National Natural Science Foundation of China[NSFC 91953203] ; National Natural Science Foundation of China[21877117] ; National Natural Science Foundation of China[82173831] ; National Natural Science Foundation of China[21907105] ; Shanghai Pujiang Program[2019PJD056] ; Science and Technology Commission of Shanghai Municipality[21ZR1475000] ; Shanghai Municipal Science and Technology Major Project |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:001043675900001 |
| 出版者 | AMER CHEMICAL SOC |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/306860]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Shen, Aijun; Lu, Xiaojie |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China 2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 3.WuXi AppTec Suzhou Co Ltd, Prot Crystallog Platform, Suzhou 215104, Peoples R China 4.Lingang Lab, Shanghai 200031, Peoples R China |
| 推荐引用方式 GB/T 7714 | Wen, Xin,Zhang, Minmin,Duan, Zhiqiang,et al. Discovery, SAR Study of GST Inhibitors from a Novel Quinazolin-4(1H)-one Focused DNA-Encoded Library[J]. JOURNAL OF MEDICINAL CHEMISTRY,2023:15. |
| APA | Wen, Xin.,Zhang, Minmin.,Duan, Zhiqiang.,Suo, Yanrui.,Lu, Weiwei.,...&Lu, Xiaojie.(2023).Discovery, SAR Study of GST Inhibitors from a Novel Quinazolin-4(1H)-one Focused DNA-Encoded Library.JOURNAL OF MEDICINAL CHEMISTRY,15. |
| MLA | Wen, Xin,et al."Discovery, SAR Study of GST Inhibitors from a Novel Quinazolin-4(1H)-one Focused DNA-Encoded Library".JOURNAL OF MEDICINAL CHEMISTRY (2023):15. |
入库方式： OAI收割
来源：上海药物研究所
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